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Comparative study of spironolactone and eplerenone in management of ascites in patients of cirrhosis of liver.
Sehgal, R, Singh, H, Singh, IP
European journal of gastroenterology & hepatology. 2020;(4):535-539
Abstract
INTRODUCTION The present study was conducted to compare the efficacy and side effects of Spironolactone and Eplerenone in management of ascites due to liver cirrhosis. MATERIALS AND METHODS 105 patients of ascites with liver cirrhosis were randomized into three groups of 35 patients each. Group I was given Spironolactone 100 mg, group II was given Eplerenone 100 mg and group III was given Eplerenone 50 mg. All patients were put on salt-restricted diet (less than or equal to 2 g of sodium) and no loop diuretics were used. Patients were followed after 7 days from the baseline and then biweekly for the period of three months and serial measurements of weight, abdominal girth and incidence of side effects especially gynecomastia, mastalgia, hyperkalemia were recorded. Results were compared. Patients having Child-Turcotte-Pugh score-C, massive ascites, hepatic encephalopathy, Hepatorenal syndrome and ascites due to cardiac, renal, malignant causes were excluded. OBSERVATIONS Difference in mean weight reduction was non significant (P = 0.964) in group I and group II whereas the difference was significant when comparison was made between Group I and III; and Group II and III (P = <0.001, <0.001, respectively). In group I, the incidence of gynecomastia was 14.28% whereas in group II and group III no case of gynecomastia was observed (P <0.001, <0.001). Hyperkalemia was present in one patient (2.8%) in group I whereas no patient developed hyperkalemia in group II and group III (P = >0.05, >0.05). CONCLUSION Eplerenone and spironolactone are equally effective in management of ascites due to liver cirrhosis but side effect profile of eplerenone scores over Spironolactone.
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Lispro insulin in people with non-alcoholic liver cirrhosis and type 2 diabetes mellitus.
Gentile, S, Guarino, G, Strollo, F, Romano, M, Genovese, S, Masarone, M, Ceriello, A
Diabetes research and clinical practice. 2016;:179-86
Abstract
AIMS: To compare metabolic control under lispro and recombinant regular human insulin (RHI) in people with diet-unresponsive type 2 diabetes mellitus (T2DM) and compensated non-alcoholic liver disease (CLD).
METHODS 108 people with T2DM and CLD were randomly allocated to RHI or lispro according to a 12+12 week cross-over protocol. A 1-week continuous glucose monitoring (CGM) session was performed at the end of each treatment period followed by a standard meal test with a 12IU lispro or RHI shot ahead.
RESULTS CGM showed higher glycemic excursions under RHI than under lispro (p<0.01) with lower glucose levels in the late post-absorption phase (p<0.05) and even more during the night (p<0.01). Post-challenge incremental areas under the curve (ΔAUC) were undistinguishable for insulin but lower for glucose, while insulin peaked higher and earlier and glycemic excursions were lower with lispro than with RHI (0.05
CONCLUSIONS Lispro granted lower early postprandial glucose levels and late postprandial hypoglycemic rates and therefore might represent the treatment of choice for people with T2DM and compensated CLD. This might depend on its faster/shorter-living effects, as well as, on the lower liver glucose output expected from its earlier hepatic distribution.
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Selenium deficiency occurs in some patients with moderate-to-severe cirrhosis and can be corrected by administration of selenate but not selenomethionine: a randomized controlled trial.
Burk, RF, Hill, KE, Motley, AK, Byrne, DW, Norsworthy, BK
The American journal of clinical nutrition. 2015;(5):1126-33
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Abstract
BACKGROUND Selenomethionine, which is the principal dietary form of selenium, is metabolized by the liver to selenide, which is the form of the element required for the synthesis of selenoproteins. The liver synthesizes selenium-rich selenoprotein P (SEPP1) and secretes it into the plasma to supply extrahepatic tissues with selenium. OBJECTIVES We conducted a randomized controlled trial to determine whether cirrhosis is associated with functional selenium deficiency (the lack of selenium for the process of selenoprotein synthesis even though selenium intake is not limited) and, if it is, whether the deficiency is associated with impairment of selenomethionine metabolism. DESIGN Patients with Child-Pugh (C-P) classes A, B, and C (mild, moderate, and severe, respectively) cirrhosis were supplemented with a placebo or supranutritional amounts of selenium as selenate (200 or 400 μg/d) or as selenomethionine (200 μg/d) for 4 wk. Plasma SEPP1 concentration and glutathione peroxidase (GPX) activity, the latter due largely to the selenoprotein GPX3 secreted by the kidneys, were measured before and after supplementation. RESULTS GPX activity was increased more by both doses of selenate than by the placebo in C-P class B patients. The activity was not increased more by selenomethionine supplementation than by the placebo in C-P class B patients. Plasma selenium was increased more by 400 μg Se as selenate than by the placebo in C-P class C patients. Within the groups who responded to selenate, there was a considerable variation in responses. CONCLUSION These results indicate that severe cirrhosis causes mild functional selenium deficiency in some patients that is associated with impaired metabolism of selenomethionine. This trial was registered at clinicaltrials.gov as NCT00271245.
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Acute effects of dipyrone on renal function in patients with cirrhosis: a randomized controlled trial.
Zapater, P, Llanos, L, Barquero, C, Bellot, P, Pascual, S, Carnicer, F, Palazón, JM, Gimenez, P, Esteban, A, Llorca, L, et al
Basic & clinical pharmacology & toxicology. 2015;(3):257-63
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Use of non-steroidal anti-inflammatory drugs in cirrhosis has been associated with impairment of renal function based on its ability to inhibit the renal production of prostaglandins. Renal effects of dipyrone in patients with cirrhosis have not been evaluated. We aimed to assess the renal effect of therapeutic doses of dipyrone used for short periods of time in patients with cirrhosis. Twenty-nine patients with cirrhosis were included in an observer-blind clinical trial. Patients were randomized to receive three times a day oral acetaminophen (500 mg; N = 15) or dipyrone (575 mg; N = 14) for 72 hr. Serum and urine samples were obtained at baseline, 48 and 72 hr, and cystatin C, creatinine, aldosterone, 6-keto-Prostaglandin-F1 alpha and prostaglandin E2 were measured. Cystatin C and creatinine levels remained comparable in patients treated with acetaminophen and dipyrone. Urine and serum prostaglandins concentrations were significantly decreased at 72 hr in patients treated with dipyrone regardless of the status of ascites. One patient with ascites treated with dipyrone required a paracentesis and developed renal insufficiency. We conclude that dipyrone and acetaminophen did not reduce renal function when used for short periods of time (up to 72 hr) in patients with cirrhosis. However, considering that dipyrone lowered renal vasodilator prostaglandins synthesis, acetaminophen appears as the safest choice with respect to kidney function in cirrhosis.
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Cardiovascular risk, lipidemic phenotype and steatosis. A comparative analysis of cirrhotic and non-cirrhotic liver disease due to varying etiology.
Loria, P, Marchesini, G, Nascimbeni, F, Ballestri, S, Maurantonio, M, Carubbi, F, Ratziu, V, Lonardo, A
Atherosclerosis. 2014;(1):99-109
Abstract
BACKGROUND Liver regulates lipid metabolism in health and disease states. Nevertheless, the entity of cardiovascular risk (CVR) resulting from dysregulation of lipid metabolism secondary to liver disease is poorly characterized. AIM AND METHODS To review, based on a PubMed literature search, the features and the determinants of serum lipid phenotype and its correlation with hepatic steatosis, insulin resistance (IR) and CVR across the wide spectrum of the most common chronic liver diseases due to different etiologies. RESULTS Alcoholic liver disease (ALD) is associated with steatosis, IR and a typical lipid profile. The relationship between alcohol intake, incident type 2 diabetes (T2D) and CVR describes a J-shaped curve. Non-alcoholic fatty liver disease (NAFLD), and probably nonalcoholic steatohepatitis (NASH) in particular, is associated with IR, atherogenic dyslipidemia and increased CVR independent of traditional risk factors. Moreover, NASH-cirrhosis and T2D contribute to increasing CVR in liver transplant recipients. HBV infection is generally free from IR, steatosis and CVR. HCV-associated dysmetabolic syndrome, featuring steatosis, hypocholesterolemia and IR, appears to be associated with substantially increased CVR. Hyperlipidemia is an almost universal finding in primary biliary cirrhosis, a condition typically spared from steatosis and associated with neither subclinical atherosclerosis nor excess CVR. Finally, little is known on CVR in patients with hepatocellular carcinoma. CONCLUSIONS CVR is increased in ALD, NAFLD and chronic HCV infection, all conditions featuring IR and steatosis. Therefore, irrespective of serum lipid phenotype, hepatic steatosis and IR may be major shared determinants in amplifying CVR in common liver disease due to varying etiology.
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Emergency anticoagulation treatment for cirrhosis patients with portal vein thrombosis and acute variceal bleeding.
Maruyama, H, Takahashi, M, Shimada, T, Yokosuka, O
Scandinavian journal of gastroenterology. 2012;(6):686-91
Abstract
OBJECTIVE To determine the safety and efficacy of anticoagulation treatment for portal vein thrombosis in cirrhosis patients with acute variceal bleeding, with patient eligibility determined by contrast ultrasonography findings. MATERIALS AND METHODS This prospective study included 23 consecutive cirrhosis patients (63.8 ± 11.8 years old, 12 males and 11 females) with emergency admission for acute variceal bleeding with or without portal vein thrombus. Eligibility for anticoagulation treatment was determined by positive intra-thrombus enhancement on contrast ultrasonography (perflubutane microbubble agent, 0.0075 mL/kg) performed before endoscopy. Low-molecular-weight heparin was administered after hemostasis was achieved by band ligation. Repeated band ligation or injection sclerotherapy combined with argon plasma coagulation was performed for variceal disappearance. RESULTS Hemostasis was achieved in all 10 patients with active bleeding. Five of these patients had portal vein thrombus, and all showed positive intra-thrombus enhancement on contrast ultrasonography. Anticoagulation treatment of these five patients resulted in complete recanalization of the portal vein within 2-11 days. There were no significant differences in the number of endoscopic treatment sessions or the length of hospital stay between the groups with and without thrombosis, and no complications including rebleeding were reported. Long term, none of the patients who continued oral anticoagulation treatment had recurrence of thrombosis (4/5). Variceal recurrence occurred only in the non-thrombosis group (2/18) during the follow-up period (median: 351 days). CONCLUSIONS Early anticoagulation treatment in cirrhosis patients with portal vein thrombosis and acute variceal bleeding may be safe, tolerated, and effective in cases with positive intra-thrombus enhancement on contrast ultrasonography.
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A pilot study of vitamin E for the treatment of cirrhotic muscle cramps.
Chandok, N, Tan, P, Uhanova, J, Shankar, N, Marotta, P
Liver international : official journal of the International Association for the Study of the Liver. 2011;(4):586-7
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Effect of varying contrast material iodine concentration and injection technique on the conspicuity of hepatocellular carcinoma during 64-section MDCT of patients with cirrhosis.
Guerrisi, A, Marin, D, Nelson, RC, De Filippis, G, Di Martino, M, Barnhart, H, Masciangelo, R, Guerrisi, I, Passariello, R, Catalano, C
The British journal of radiology. 2011;(1004):698-708
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OBJECTIVES The aim of this study was to compare the intraindividual effects of contrast material with two different iodine concentrations on the conspicuity of hepatocellular carcinoma (HCC) and vascular and hepatic contrast enhancement during multiphasic, 64-section multidetector row CT (MDCT) in patients with cirrhosis using two contrast medium injection techniques. METHODS Patients were randomly assigned to one of two groups with an equal iodine dose but different contrast material injection techniques: scheme A, fixed injection duration (25 s), and scheme B, fixed injection flow rate (4 ml s(-1)). For each group, patients were randomised to receive both moderate-concentration contrast medium (MCCM) and high-concentration contrast medium (HCCM) during two CT examinations within 3 months. Enhancement of the aorta, liver and portal vein and the tumour-to-liver contrast-to-noise ratio (CNR) were compared between MCCM and HCCM. RESULTS 30 patients (mean age 59 years; range 45-80 years; 16 patients in scheme A and 14 in scheme B) with a total of 31 confirmed HCC nodules were prospectively enrolled. For scheme B, the mean contrast enhancement of the aorta and tumour-to-liver CNR were significantly higher with HCCM than with MCCM during the hepatic arterial phase (+350.5 HU vs +301.1 HU, p = 0.001, and +7.5 HU vs +5.5 HU, p = 0.004). For both groups, there was no significant difference between MCCM and HCCM for all other comparisons. CONCLUSION For a constant injection flow rate, HCCM significantly improves the conspicuity of HCC lesions and aortic enhancement during the hepatic arterial phase on 64-section MDCT in patients with cirrhosis.
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[Approach to the patient with zirrhotic ascites--no diagnosis without a tap].
Umgelter, A
MMW Fortschritte der Medizin. 2010;(42):36-8
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Portal-systemic encephalopathy in a randomized controlled trial of endoscopic sclerotherapy versus emergency portacaval shunt treatment of acutely bleeding esophageal varices in cirrhosis.
Orloff, MJ, Isenberg, JI, Wheeler, HO, Haynes, KS, Horacio, JB, Rapier, R, Vaida, F, Hye, RJ
Annals of surgery. 2009;(4):598-610
Abstract
BACKGROUND In patients with cirrhosis and bleeding esophageal varices, there is a widespread belief that control of bleeding by portal-systemic shunts is compromised by a high incidence of shunt-related portal-systemic encephalopathy (PSE). This important issue was examined by a randomized controlled trial that compared emergency and long-term endoscopic sclerotherapy (EST) to emergency direct portacaval shunt (EPCS) in patients with cirrhosis and acute variceal hemorrhage. METHODS The study was a community-wide undertaking known as the San Diego Bleeding Esophageal Varices Study. A total of 211 unselected, consecutive patients with biopsy-proven cirrhosis and endoscopically proven, acutely bleeding esophageal varices that required at least 2 units of blood transfusion were randomized to EST (n = 106) or EPCS (n = 105). The diagnostic workup was completed in less than 6 hours and EST or EPCS was initiated within 8 hours of initial contact. Long-term EST was performed according to a deliberate schedule over months. Criteria for failure of EST or EPCS were clearly defined and crossover rescue treatment was applied, whenever possible, when failure of primary therapy was declared. PSE was quantitated by a "blinded" senior faculty gastroenterologist. Four variously weighted components of PSE were graded on a scale of 0 to 4: (1) mental state, (2) asterixis, (3) number connection test, and (4) arterial blood ammonia. PSE was classified as recurrent if 2 or more episodes were documented. All patients (100%) had follow-up for more than 9.4 years or until death. RESULTS Child's risk classes in the EST and EPCS groups, respectively, were 25% and 30% in class A, 43% and 47% in class B, and 26% and 29% in class C. Mean time from onset of bleeding to EST or EPCS was less than 24 hours, and from study entry to EST or EPCS was 3.1 to 4.4 hours, respectively. EST achieved permanent control of bleeding in only 20% of patients, while EPCS permanently controlled bleeding in every patient (P ≤ 0.001). Survival following EPCS was 3.5 to 5 times greater than that of EST at 5, 10, and 15 years (P ≤ 0.001). The incidence of recurrent PSE following EST (35%) was more than twice the incidence following EPCS (15%) (P ≤ 0.001). EST patients had a total of 179 episodes of PSE and 146 PSE-related hospital admissions, compared with EPCS patients who had 94 episodes of PSE and 87 hospital admissions (P ≤ 0.001). Recurrent upper gastrointestinal bleeding, which was rare in the EPCS group, was a major causative factor of PSE in the EST patients. CONCLUSIONS In contrast to EST, EPCS permanently controlled variceal bleeding, resulted in significantly greater long-term survival, and was followed by a relatively low (15%) incidence of PSE. These results were facilitated by rigorous, frequent, and lifelong follow-up that included regular counseling on dietary protein restriction and abstinence from alcohol, and by long-term patency of the portacaval shunt in 98% of patients. Furthermore, these results call into question the practice of avoiding portacaval shunt because of fear of PSE, and thereby foregoing the lifesaving advantage achieved by surgical control of bleeding. (clinicaltrials.gov NCT00690027).